Beneficial Effects Research Articles

The Possible Roles of β-alanine and L-carnosine in Anti-aging.

alanine (BA), being a non-proteinogenic amino acid, is an important constituent of L-carnosine (LC), which is necessary for maintaining the muscle buffering capacity and preventing a loss of muscle mass associated with aging effects. BA is also very important for normal human metabolism due to the formation of a part of pantothenate, which is incorporated into coenzyme A. BA is synthesized in the liver, and its combination with histidine results in the formation of LC, which accumulates in the muscles and brain tissues and has a well-defined physiological role as a good buffer for the pH range of muscles that caused its rapidly increased popularity as ergogenic support to sports performance. The main antioxidant mechanisms of LC include reactive oxygen species (ROS) scavenging and chelation of metal ions. With age, the buffering capacity of muscles also declines due to reduced concentration of LC and sarcopenia. Moreover, LC acts as an antiglycation agent, ultimately reducing the development of degenerative diseases. LC has an anti-inflammatory effect in autoimmune diseases such as osteoarthritis. As histidine is always present in the human body in higher concentrations than BA, humans have to get BA from dietary sources to support the required amount of this critical constituent to supply the necessary amount of LC synthesis. Also, BA has other beneficial effects, such as preventing skin aging and intestinal damage, improving the stress-- fighting capability of the muscle cells, and managing an age-related decline in memory and learning. In this review, the results of a detailed analysis of the role and various beneficial properties of BA and LC from the anti-aging perspective.

Grief and delivering a statement in court: a longitudinal mixed-method study among homicidally bereaved people

ABSTRACT Background: Participating in a criminal trial may increase the likelihood of developing psychopathology. In 2021, people bereaved by a plane disaster (flight MH17) had the opportunity to deliver a victim personal statement (VPS) in Dutch court. Objective: This longitudinal mixed-method study examined different aspects of 84 bereaved people’s experiences with VPS delivery. Method: Motivations to deliver, or not deliver, an oral VPS were examined qualitatively using thematic content analysis. Whether background and loss-related variables were related to the decision to deliver a VPS was examined using binary logistic regression analyses. Between-group (delivered VPS vs. did not) and within-group (pre- vs. post-VPS) comparisons were made regarding prolonged grief disorder (PGD), posttraumatic stress disorder (PTSD), and depression levels using t-tests and paired t-tests. Results: Bereaved people were most frequently motivated to deliver an oral VPS to describe the impact of the incident, while those who did not deliver an oral VPS commonly wanted to protect themselves from the perceived emotional burden. None of the correlates – i.e. biological sex, age, level of education, number of losses, and (closest) relationship to the deceased – were related to the decision to deliver a VPS. Lastly, significantly higher PGD, PTSD, and depression levels were reported by people who delivered a VPS than those who did not, before and after the court hearing. No significant within-group differences were found over time. Conclusions: Professionals may provide emotional support to bereaved people who want to deliver a VPS and manage their expectations if they want to deliver a VPS for the purpose of symptom reduction. Future research may benefit from examining other ways in which VPS delivery might have beneficial or detrimental effects for specific individuals. Overall, implementing VPS delivery in court on the basis of emotional restoration remains empirically unsupported, if defined as a reduction in psychopathological levels.

“It takes a lot of sisu to get through it”- managerial experiences of facing adversities during pandemic

ABSTRACTPurposeSisu refers to extraordinary internal strength in the face of adversities. Although originally a Finnish concept, it can be a universally useful concept for studying managerial well-being and performance during difficult or even emergency periods. Previous research on sisu categorizes it into beneficial and harmful sisu and suggests that these two dimensions of sisu are useful when studying determination and resoluteness in crisis situations. This study applies the concept of sisu to examine managers’ well-being in times of crisis.MethodologyInterviews were conducted with 15 managers in the hotel, manufacturing and retail industries in Finland.ResultsThe beneficial effects of sisu seem to dissolve when it is used too often. The study also highlighted the paradoxical tension involved in the decision to stop or continue actions in a difficult situation and contributes to sisu research by discussing collective sisu.ConclusionThe results of this study suggest that beneficial sisu helps to overcome adversity, while harmful sisu causes distortions in thinking that are detrimental to managers. Understanding one’s own tendency towards beneficial or harmful sisu in difficult situations can help in managerial work. Collective sisu is an excellent resource for overcoming difficult situations in workplaces.

INFLUENCE OF UROGENEITRAL INFECTION IN PREGNANT WOMEN ON THE UTERINE – FETOPLACENTARY COMPLEX

As reported by the World Health Organization (WHO), approximately 20 % of pregnant women globally are aff ected by an infection of the lower genital tract. Urogenital infection can result in complications during the onset and progression of pregnancy, as well as the postpartum period. These complications include placental dysfunction, premature birth, low birth weight, premature rupture of the fetal membranes, and postpartum endometritis. A marker of normal placental function is α2-fertility microglobulin (AFMG), the determination of which will refl ect the presence or absence of a uterine- fetoplacental complex violation during urogenital infection in pregnant women.The aim of the study is to reveal the infl uence of urogenital infection on the dysfunction of the uterine – fetoplacental complex in pregnant women.Materials and methods. A total of 75 pregnant women were examined, divided into two groups: the main group (MG) and the comparison group (CG). The MG consisted of 55 pregnant women, of whom 35 underwent local sanitation of the urogenital infection according to the identifi ed pathogen (Subgroup A) and 20 refused this procedure (Subgroup B). The CG consisted of 20 pregnant women without urogenital infection, as determined by bacterioscopic, bacteriological, and polymerase chain reaction (PCR) examinations. All pregnant women underwent determination of AFMG in blood serum via immunoenzymatic methodology. The statistical analysis was conducted using the MedStat software (serial number MS00019). The study was performed in accordance with the provisions of the Declaration of Helsinki. The study protocol was approved by the Local Ethics Committee of PFMU for all women who participated in this study. Statistical processing was performed using the MedStat program (serial number MS00019). The work is a part of the initiative research work of the Department of Obstetrics and Gynecology No. 1 of Poltava State Medical University «Pathogenetic role of endothelial dysfunction and genetic features in pathology during pregnancy and gynecological diseases» (state registration No. 0117U005253, term of implementation 2017-2023).Research results. The results of the study demonstrated that pregnant women with a urogenital infection had a history of chronic pyelonephritis 5.5 times more frequently (p = 0.03) and salpingo- oophoritis 10.2 times more frequently (p < 0.001), which may be a source of latent infection. The most prevalent infectious agents among pregnant women were: The most prevalent microorganisms were Ureaplasma urealyticum (21.4 %), Candida fungi (19.04 %), Gardnerella vaginalis (11.9 %), and Toxoplasma gondii (11.9 %). The level of AFMG in pregnant women with urogenital infection was observed to be 4.3 times lower than in pregnant women with CG (p < 0.001). The remediation of an infection of the lower genital tract during pregnancy has been observed to increase AFMG production by a factor of four (p < 0.001). The level of AFMG in pregnant women of CG was 2.2 times higher than in pregnant womenof Subgroup A (p < 0.004).Conclusions. It was demonstrated that urogenital infection in pregnant women has a considerable impact on the dysfunction of the utero- fetoplacental complex. It was also shown that local sanitation of the lower genital tract in these women, based on the identified pathogen, has a benefi cial eff ect on the placenta’s functioning. However, this approach does not fully address the issue of protein synthesis impairment.

The Landscape of Randomized Clinical Trial Meta-analyses on Statins for Aneurysmal Subarachnoid Hemorrhage: A Scoping Review.

Aneurysmal subarachnoid hemorrhage (aSAH) is a type of non-traumatic SAH that can have detrimental effects on the central nervous system, resulting in severe disability or death. Early nimodipine is currently the only strongly recommended pharmacological treatment that has shown efficacy in improving neurological/functional outcomes in aSAH patients. Whether statin treatment is of benefit to aSAH patients is an issue that has generated considerable interest and debate. In the present scoping review, we mapped and analyzed the available literature on metaanalyses of randomized clinical trials (RCTs) examining the effect of statins on aSAH. Seventeen meta-analyses of RCTs, published between 2008 and 2023, were identified. Treatments in included meta-analyses were based on various regimens of simvastatin, pravastatin, pitavastatin or atorvastatin for up to 21 days. Eleven of the included reports indicated some beneficial effect of statin treatment, reducing rates of at least one of the following: cerebral vasospasm, delayed cerebral ischemia/delayed ischemic neurologic deficit, mortality or functional/ neurological outcome. In contrast, six meta-analyses, showed no such effects. The limitations reported by several meta-analyses, included low patient numbers or disproportionate representation of patients from certain RCTs, differences in drug treatment, patient diagnostic criteria and outcome evaluation between RCTs, as well as poor data quality or lack of RCTs data. Knowledge of the reported limitations may aid the design of future clinical trials and/or their meta-analyses.

Comparison Among Food By-Products to Improve the Shelf Life of a Fresh Burger Based on Shelled Shrimps.

Pomegranate peels, fig peels, and by-products from turnip greens were used as novel ingredients in burgers based on shelled shrimps. With the aim, a control without any by-products and three fortified samples with 7.5% (w/w) by-product were realized. To verify the benefic effects of by-product addition on the chemical quality of burgers, total phenols, total flavonoids, and antioxidant activity were measured in both the control and fortified samples. In addition, during storage under refrigerated conditions, the microbiological proliferation of the main spoilage bacteria, the pH, and the sensory acceptability were properly monitored in all the samples. Results from chemical analyses confirmed that the nutritional level of shrimp-based burgers enriched with by-products was better than that of the control. Burgers with peels from pomegranate recorded the best results (2.67 ± 0.24 mg GAE/g dw, 1.62 ± 0.21 mg QE/g dw, and 12.63 ± 0.41 mg Trolox/g dw for total phenols, flavonoids, and antioxidant activity, respectively). From the microbiological point of view, the bacterial proliferation was always more rapid in the control than in the other samples. Among the by-products, the pomegranate peels better delayed the spoiling phenomena, even though mesophilic and psychrotrophic bacteria grew abundantly and rapidly in all the products, thus reducing the differences among samples. All the burgers maintained sensory acceptability for more than two weeks, regardless of the by-product addition. Considering both microbiological stability and sensory properties, the shelf life of this product was calculated to be around 1 week for the control burger, 8.5 days for both burgers with fig peels and by-products from turnip greens, and 9 days for the shrimp-based burger fortified with pomegranate peels.

Intravenous alteplase before endovascular therapy for acute large vessel occlusion with large ischemic core: subanalysis of a randomized clinical trial

BackgroundThe efficacy of endovascular therapy (EVT) in patients with large ischemic core has been reported, but it remains unclear whether IV alteplase (IVT) has beneficial effects in addition to EVT...

Monocrotaline-induced pulmonary arterial hypertension: the benefic effects of magnesium sulfate, Rosuvastatin and Sildenafil.

Pulmonary arterial hypertension (PAH) is characterized by several maladaptive mechanisms: endothelial dysfunction, oxidative stress, inflammation, pathological remodeling of the pulmonary arterioles, and cellular hypoxia. These mechanisms all favor progressive pulmonary vasculopathy and progressive right ventricle (RV) dysfunction. This study aims to characterize the experimental model of monocrotaline-induced PAH in rats. Subsequently, by administering Sildenafil, Rosuvastatin, and Magnesium sulfate, we assessed the animals via ultrasonography and assayed biochemical parameters to evaluate the efficacy of the treatment. 42 male Wistar rats were randomly allocated into six equal groups (n=7) and received a single subcutaneous MCT injection (60 mg/kg dose). Drug therapy with Sildenafil, Rosuvastatin, and Magnesium sulfate in different combinations was initiated 14 days after MCT injection. Fulton Index, RV anterior wall thickness, RV internal diameter, and pulmonary arterial acceleration time/ejection time (PAAT/PAET) were measured. The following biochemical parameters were also measured: endothelin 1(ET1), brain natriuretic peptide (BNP), nitric oxide (NO) metabolites, vascular endothelial growth factor (VEGF), and inducible nitric oxide synthase (iNOS). MCT-PAH was a successful experimental model that has fulfilled anatomical, pressure, and biochemical characteristics supporting this fact. Sildenafil monotherapy does not provide any substantial benefit in reducing MCT-PAH. The additive effects of Rosuvastatin + Sildenafil or Sildenafil + Magnesium sulfate significantly reduced the degree of RV hypertrophy and improved RV systolic pressures. However, there were also modest decreases in biochemical parameters compared to Sildenafil alone. The triple drug combination Sildenafil + Rosuvastatin + Magnesium sulfate shows significant results (p<0,001) compared to the previously described drug combinations. The lowest biochemical parameters were recorded: RV anterior wall thickness, RV internal diameter values, and a significant PAAT/PAET ratio improvement. Thanks to their benefits on vascular pathological remodeling, triple drug combinations implicitly reduce ET1, VEGF, NO metabolites, and iNOS values with statistical significance. The beneficial pleiotropic effects of Rosuvastatin combined with Magnesium sulfate (thanks to its potent vasodilator and antioxidant effects) demonstrated its efficacy in this study by improving RV systolic pressures, RV hypertrophy, oxidative stress, and myocardial dysfunction biomarkers.

The Antidiabetic Drug Metformin Attenuated Depressive and Anxietylike Behaviors and Oxidative Stress in the Brain in a Rodent Model of Inflammation Induced by Lipopolysaccharide in Male Rats.

Inflammation is considered to be a link between diabetes and central nervous system (CNS) disorders, including depression and anxiety. Metformin is suggested to have antioxidant, anti-inflammatory, and mood-improving effects. The aim of the current research was to investigate the effects of the antidiabetic drug metformin on depressive- and anxiety- like behaviors and oxidative stress in the brain in a rodent model of inflammation induced by lipopolysaccharide (LPS) in male rats. The rats were treated as follows: (1) Vehicle instead of metformin and lipopolysaccharide, (2) Lipopolysaccharide (1 mg/ kg) + vehicle instead of metformin, (3-5) Lipopolysaccharide + 50, 100, or 150 mg/ kg of metformin. After the behavioral tests, including open field (OF), elevated pulse maze (EPM), and force swimming (FS) tests, the brains were removed, and malondialdehyde (MDA), nitric oxide (NO) metabolites, total thiol, catalase (CAT) activity, interleukin-6 (IL-6) and superoxide dismutase (SOD) activity were determined. In the EPM, metformin increased the open arm time and entry and decreased closed arm time and entry. In the FS test, metformin lowered the immobility and increased active time compared to lipopolysaccharide. In the OF test, metformin increased total crossing and total distance, time spent, traveled distance, and crossing number in the central zone. As a result of metformin administration, IL-6, MDA, and NO metabolites were decreased while thiol content, SOD, and CAT activity were increased. The results indicated that the well-known antidiabetic drug metformin attenuated depressive- and anxiety-like behaviors induced by inflammation in rats. These beneficial effects are suggested to be due to their attenuating effects on neuroinflammation, oxidative stress, and NO in the brain.

Murraya koenigii (Curry Tree): A review of its Phytochemistry, Ethnomedicinal uses, and Pharmacology with Respect to Molecular Mechanisms

Abstract: Medicinal plants have significant therapeutic value and are a gift to humanity in pursuing healthy living. The discovery of numerous rejuvenating compounds that can stop or reduce the pathology of many diseases will be a crucial advancement in the coming years. Synthetic compounds can cause health issues and side effects, necessitating the development of molecules derived from plants and other natural resources as viable substitutes for synthetic compounds. Several plant phytochemicals and extracts have been found to have significant effects on traditional medical therapy. Murraya koenigii (M. Koenigii) is a member of the Rutaceae family, well-known in the Ayurvedic system of medicine as a therapeutically important herb of Indian origin. M. Koenigii has been used in several ancient systems of medicine, including Siddha and Unani, as a multi-potential medicinal plant. Previous research has shown that this plant's bark, roots, and leaves are abundant sources of carbazole alkaloids, which have beneficial pharmacological and biological effects. These include antioxidant, antibacterial, antidiabetic, anti-inflammatory, antihypertensive, antifungal, antiprotozoal, hepatoprotective, antihypercholesterolemic, antiulcer, cytotoxic, antidiarrheal, phagocytic, neuroprotective, and antitumor activities. The key components of the M. koenigii plant and their pharmacological activities against various diseases using preclinical models are discussed in this review. Exhaustive studies on the molecular mechanism of action of M. koenigii are needed to validate the effectiveness of curry tree and their constituents as potent therapeutic agents. However, serious efforts are required to identify, isolate and evaluate the chemical components for nutritional and medicinal potentials.

Neural precursor cells rescue symptoms of Rett syndrome by activation of the Interferon γ pathway.

The beneficial effects of Neural Precursor Cell (NPC) transplantation in several neurological disorders are well established and they are generally mediated by the secretion of immunomodulatory and neurotrophic molecules. We therefore investigated whether Rett syndrome (RTT), that represents the first cause of severe intellectual disability in girls, might benefit from NPC-based therapy. Using in vitro co-cultures, we demonstrate that, by sensing the pathological context, NPC-secreted factors induce the recovery of morphological and synaptic defects typical of Mecp2 deficient neurons. In vivo, we prove that intracerebral transplantation of NPCs in RTT mice significantly ameliorates neurological functions. To uncover the molecular mechanisms underpinning the mediated benefic effects, we analyzed the transcriptional profile of the cerebellum of transplanted animals, disclosing the possible involvement of the Interferon γ (IFNγ) pathway. Accordingly, we report the capacity of IFNγ to rescue synaptic defects, as well as motor and cognitive alterations in Mecp2 deficient models, thereby suggesting this molecular pathway as a potential therapeutic target for RTT.

Influence of stress-specific interventions on biomarker levels and cognitive function in cancer patients: Systematic review and meta-analysis.

Cancer patients' psycho-physiological health is seriously affected by long-term exposure to stress. Many studies have explored the impact of stress-specific interventions on cancer patients' biomarker levels and cognitive functions. However, the current research findings are inconsistent, and their statistical power is limited by the small samples. Therefore, we conducted this meta-analysis to verify the effect of stress-specific interventions on cancer patients. The literature involved nine databases from the inception until January 13, 2024, extracted 19 randomized controlled trials (RCTs). Review Manager (RevMan) 5.4 software was used to perform a meta-analysis, and the revised Cochrane risk of bias tool (RoB2) was utilized for quality evaluation. Nine RCTs were assessed as having a low risk of bias, and others had a moderate risk. The results showed that stress-specific interventions had beneficial effects on patients' subjective cognition but uncertain impacts on their executive function, tumour necrosis factor-α level, morning cortisol level, and no effect on cortisol at other times, interleukin (IL)-10, IL-8, IL-6, IL-1, and C-reactive protein. More rigorous studies are required to elucidate the influence of stress-specific interventions on biomarker levels. The potential mechanism by which stress-specific interventions affect the cancer patient's cognitive function remains unclear.

The Role of Gut Microbiota and Associated Compounds in Cardiovascular Health and its Therapeutic Implications.

It is possible that gut bacteria may have a beneficial effect on cardiovascular health in humans. It may play a major role in the progression of a variety of cardiovascular diseases, including Heart Failure (HF), Atherosclerosis, Coronary Arterial Disease (CAD), Ischemic Heart Disease (IHD), and Others. Dysbiosis of the gut microbiota, along with its direct and indirect impact on gut health, may induce cardiovascular disorders. Although advanced studies have demonstrated the relationship of various metabolites to cardiovascular diseases (CVD) in animals, translating their functional capacity to humans remains a significant area of research. This paper simplifies the demonstration of some compounds, pathways, and components like Trimethylamine N-oxide (TMAO), short-chain fatty acids (SCFAs), and butyrate production. It demonstrates how a change in eating habits causes TMAO and how the impact of different drugs on gut microbiota species and high consumption of Westernized food causes several heartrelated problems, such as atherosclerosis and inflammation that can even become the cause of heart failure. Modulation of the gut microbiome, on the other hand, is a novel therapeutic measure because it can be easily altered through diet and other lifestyle changes. It could then be used to lower the risk of several CVDs.

A Critical Assessment of Remdesivir

Abstract: The COVID-19 pandemic that originated in Wuhan city, China, has affected every village in India. This has killed millions of people. This disease involves symptomatic and asymptomatic mutations. The purpose of this review was to assess the effectiveness of remdesivir particularly against SAR-CoV-2 (Coronaviridae family). The relevant works have been studied with respect to the drug's chemistry, mechanism of action, pharmacokinetics, pharmacodynamics, clinical data, and side effects. Remdesivir has been used in many cases of coronavirus-infected patients because it has been proven to possess beneficial effects; however, significant adverse effects have also been reported. Remdesivir has been reported to help in lowering the disease's high fatality rate. However, the WHO has warned against using the medicine because there is no clinical data to support its therapeutic efficacy.

The miR-210 Primed Endothelial Progenitor Cell Exosomes Alleviate Acute Ischemic Brain Injury.

Stem cell-released exosomes (EXs) have shown beneficial effects on regenerative diseases. Our previous study has revealed that EXs of endothelial progenitor cells (EPC-EXs) can elicit favorable effects on endothelial function. EXs may vary greatly in size, composition, and cargo uptake rate depending on the origins and stimulus; notably, EXs are promising vehicles for delivering microRNAs (miRs). Since miR-210 is known to protect cerebral endothelial cell mitochondria by reducing oxidative stress, here we study the effects of miR-210-loaded EPC-EXs (miR210-EPC-EXs) on ischemic brain damage in acute ischemic stroke (IS). The miR210-EPC-EXs were generated from EPCs transfected with miR-210 mimic. Middle cerebral artery occlusion (MCAO) surgery was performed to induce acute IS in C57BL/6 mice. EPC-EXs or miR210-EPC-EXs were administrated via tail vein injection 2 hrs after IS. To explore the potential mechanisms, inhibitors of the vascular endothelial growth factor receptor 2 (VEGFR2)/PI3 kinase (PI3K) or tyrosine receptor kinase B (TrkB)/PI3k pathways were used. The brain tissue was collected after treatments for infarct size, cell apoptosis, oxidative stress, and protein expression (VEGFR2, TrkB) analyses on day two. The neurological deficit score (NDS) was evaluated before collecting the samples. 1) As compared to EPC-EXs, miR210-EPC-EXs profoundly reduced the infarct volume and improved the NDS on day two post-IS. 2) Fewer apoptosis cells were detected in the peri-infarct brain of mice treated with miR210-EPC-EXs than in EPC-EXs-treated mice. Meanwhile, the oxidative stress was profoundly reduced by miR210-EPC-EXs. 3) The ratios of p-PI3k/PI3k, p- VEGFR2/VEGFR2, and p-TrkB/TrkB in the ipsilateral brain were raised by miR210-EPC-EXs treatment. These effects could be significantly blocked or partially inhibited by PI3k, VEGFR2, or TrkB pathway inhibitors. These findings suggest that miR210-EPC-EXs protect the brain from acute ischemia- induced cell apoptosis and oxidative stress partially through the VEGFR2/PI3k and TrkB/PI3k signal pathways.

Effects of Glucosamine in the Temporomandibular Joint Osteoarthritis: A Review.

Osteoarthritis in the temporomandibular joint (TMJ) is a chronic disease characterized by irreversible damage to articular surfaces, including inflammation, loss of articular cartilage, and subchondral bone alterations, which would be radiographically evident only in later stages. Symptomatic slow-acting so-called nutraceutical drugs have been proposed as a treatment for osteoarthritis in comparison to non-steroidal anti-inflammatory drugs (NSAID) because of their appreciable safety profile even in long-term intake. Glucosamine, being one among them, proved highly efficient in knee osteoarthritis. However, its application in TMJ osteoarthritis dates back only to 2001 and is still inconclusive in its efficiency even with systematic reviews, in restoring the structural and functional aspects of damaged TMJ. Glucosamine, being a natural compound and also a contributor to building the matrix of articular cartilage, can be utilized effectively for TMJ osteoarthritis as an adjunct along with other conventional treatment modalities available till now, which also have moderate prognosis in most of the clinical scenarios. This review summarizes data relating to the mechanism of osteoarthritis and its management using glucosamine formulations. The beneficial effects of glucosamine on the pathophysiology of TMJ osteoarthritis are possibly due to its contribution to hyaluronic acid regulation and in establishing a proper balance between anabolism/catabolism in the articular tissues.

Benefits of dark chocolate intake on retinal vessels functionality: a randomized, blind, crossover clinical trial

There is a lack of knowledge about the effect of flavanols-rich dark chocolate intake on the anatomy and functionality of retinal vessels. The aim of this study prospective, randomized, blind, crossover clinical trial (ClinicalTrials.gov Identifier: NCT05227248, 07/02/2022) was to evaluate the effect of dark-chocolate intake on the functionality and anatomy of the retinal vessels in healthy subjects using dynamic vessel analyzer (DVA) and optical coherence tomography angiography (OCT-A). Twenty eyes of 20 healthy subjects (mean age, 24.4 ± 1.6 years; 12 females) were enrolled. Participants were randomized to consume 20 g of dark chocolate or 7.5 g of milk chocolate. Visual function, DVA and OCT-A parameters were evaluated before chocolate consumption and two hours later. One week later, the same participants were tested before and after consuming the opposite chocolate. Using OCT-A, no differences were disclosed in terms of perfusion density changes after dark-chocolate and milk-chocolate intake analyzing all chorioretinal plexuses (p > 0.09 in all analyses). Using DVA, a significant increase in the arterial dilation percentage after flicker stimulation was disclosed comparing baseline (2.750 ± 2.054%) with values after the dark chocolate intake (4.145 ± 3.055%, p = 0.016). This difference was not disclosed after the milk chocolate intake (p = 0.465). We disclosed that a reasonable amount of flavanols-rich chocolate in healthy subjects has benefic functional short-term effects in retinal vessels measured with DVA. This suggests a potential role of dark chocolate intake on retinal vessels. Further studies with long-term follow-up are warranted to show if the chronic assumption of dark chocolate could play a favorable role in the prevention of retinal diseases.

Sympathetic Motor Neuron Dysfunction is a Missing Link in Age-Associated Sympathetic Overactivity.

Overactivity of the sympathetic nervous system is a hallmark of aging. The cellular mechanisms behind this overactivity remain poorly understood, with most attention paid to likely central nervous system components. In this work, we hypothesized that aging also affects the function of motor neurons in the peripheral sympathetic ganglia. To test this hypothesis, we compared the electrophysiological responses and ion-channel activity of neurons isolated from the superior cervical ganglia of young (12 weeks), middle-aged (64 weeks), and old (115 weeks) mice. These approaches showed that aging does impact the intrinsic properties of sympathetic motor neurons, increasing spontaneous and evoked firing responses. A reduction of M current emerged as a major contributor to age-related hyperexcitability. Thus, it is essential to consider the effect of aging on motor components of the sympathetic reflex as a crucial part of the mechanism involved in sympathetic overactivity.

Comparative pharmacokinetic investigation on crocetin in hyperlipidemia and normal rats after oral administration.

Crocetin as one of the main components of saffron possesses a lot of pharmacological effects, especially the beneficial effects in the treatment of hyperlipidemia. However, the pharmacokinetics of crocetin in the pathological state of hyperlipidemia has not been reported. In present study, the pharmacokinetics of crocetin in hyperlipidemia rats after oral administration of crocetin was investigated and the possible mechanisms for the pharmacokinetics were explored. High-fat diet was used to induce hyperlipidemia in rats. The pharmacokinetics of crocetin was investigated in hyperlipidemia and normal rats after oral and intravenous administration of crocetin, and the possible mechanisms of the pharmacokinetic changes were investigated in terms of metabolism and absorption using in vitro incubation with liver microsomes and the everted gut sac method, respectively. Results indicated that the AUCs of crocetin in hyperlipidemia rats after oral administration of crocetin were remarkably decreased when compared with those in normal rats. Moreover, crocetin was also metabolized more rapidly in the liver microsomes of hyperlipidemia rats and intestinal absorption of crocetin was significantly reduced in hyperlipidemia rats. It suggested that the remarkably decreased AUCs of crocetin in hyperlipidemia rats might partly result from the result of faster metabolic elimination and reduced absorption of crocetin in the hyperlipidemia pathological state. And the present investigations conducted on rats demonstrate that further investigations into the kinetics of crocetin in humans with hyperlipidemia are necessary in order to ensure an adequate dosage in this indication.

Modulating Mitochondrial Dynamics Mitigates Cognitive Impairment in Rats with Myocardial Infarction.

We have previously demonstrated that oxidative stress and brain mitochondrial dysfunction are key mediators of brain pathology during myocardial infarction (MI). To investigate the beneficial effects of mitochondrial dynamic modulators, including mitochondrial fission inhibitor (Mdivi-1) and mitochondrial fusion promotor (M1), on cognitive function and molecular signaling in the brain of MI rats in comparison with the effect of enalapril. Male rats were assigned to either sham or MI operation. In the MI group, rats with an ejection Fraction less than 50% were included, and then they received one of the following treatments for 5 weeks: vehicle, enalapril, Mdivi-1, or M1. Cognitive function was tested, and the brains were used for molecular study. MI rats exhibited cardiac dysfunction with systemic oxidative stress. Cognitive impairment was found in MI rats, along with dendritic spine loss, blood-brain barrier (BBB) breakdown, brain mitochondrial dysfunction, and decreased mitochondrial and increased glycolysis metabolism, without the alteration of APP, BACE-1, Tau and p-Tau proteins. Treatment with Mdivi-1, M1, and enalapril equally improved cognitive function in MI rats. All treatments decreased dendritic spine loss, brain mitochondrial oxidative stress, and restored mitochondrial metabolism. Brain mitochondrial fusion was recovered only in the Mdivi-1-treated group. Mitochondrial dynamics modulators improved cognitive function in MI rats through a reduction of systemic oxidative stress and brain mitochondrial dysfunction and the enhancement of mitochondrial metabolism. In addition, this mitochondrial fission inhibitor increased mitochondrial fusion in MI rats.